Chronic Kidney Disease (CKD) is ongoing damage of the kidneys, which affects their ability to filter the blood the way they should. Worldwide CKD is considered as the 16th leading cause of death and affects 8% - 16% of the population. CKD often goes unnoticed and is revealed as an incidental finding. Healthcare providers diagnose the condition as CKD based on persistent abnormal kidney function tests revealing kidney damage markers > 3 months, urine albumin creatinine ratio (UACR) > or equal to 30 mg/g per 24 hours, and GFR < 60 mL/min/1.73m 2 . In this article, we have discussed chronic kidney disease in terms of kidney physiology, chronic kidney disease pathophysiology, etiology, diagnosis, signs and symptoms, and management.
KeywordsChronic Kidney DiseaseStages of Chronic Kidney DiseaseDiagnosis of Chronic Kidney DiseaseChronic Kidney Disease ManagementPhysiology of KidneysPathophysiology of KidneysRenal Replacement Therapy
Jha, V., Garcia-Garcia, G., Iseki, K., et al. (2013) Chronic Kidney Disease: Global Dimension and Perspectives. Lancet, 382, 260-272. https://doi.org/10.1016/S0140-6736(13)60687-X
Slifer, S., et al. (2013) KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Vol. 3, National Kidney Foundation. https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf
Ogobuiro, I. and Tuma, F. (2023) Physiology, Renal. In: StatPearls, StatPearls Publishing, Treasure Island. https://pubmed.ncbi.nlm.nih.gov/30855923/
Rayner, H., Thomas, M. and Milford, D. (2016) Kidney Anatomy and Physiology. In: Understanding Kidney Diseases, Springer, Cham, 1-10. https://link.springer.com/chapter/10.1007/978-3-319-23458-8_1
Matovinović, M.S. (2009) Pathophysiology and Classification of Kidney Diseases. eJIFCC: Electronic Journal of the International Federation of Clinical Chemistry and Laboratory Medicine, 20, 2-11.
Ren, J. and Dai, C. (2020) Pathophysiology of Chronic Kidney Disease. In: Yang, J. and He, W., Eds., Chronic Kidney Disease, Springer, Singapore, 13-32. https://link.springer.com/chapter/10.1007/978-981-32-9131-7_2
Grams, M.E., et al. (2016) Race, APOL1 Risk, and eGFR Decline in the General Population. Journal of the American Society of Nephrology, 27, 2842-2850. https://doi.org/10.1681/ASN.2015070763
Peralta, C.A., et al. (2016) APOL1 Genotype and Race Differences in Incident Albuminuria and Renal Function Decline. Journal of the American Society of Nephrology, 27, 887-893. https://doi.org/10.1681/ASN.2015020124
Foster, M.C., et al. (2013) APOL1 Variants Associate with Increased Risk of CKD among African Americans. Journal of the American Society of Nephrology, 24, 1484-1491. https://doi.org/10.1681/ASN.2013010113
Kopp, J.B., et al. (2011) APOL1 Genetic Variants in Focal Segmental Glomerulosclerosis and HIV-Associated Nephropathy. Journal of the American Society of Nephrology, 22, 2129-2137. https://doi.org/10.1681/ASN.2011040388
Parsa, A., et al. (2013) APOL1 Risk Variants, Race, and Progression of Chronic Kidney Disease. The New England Journal of Medicine, 369, 2183-2196. https://doi.org/10.1056/NEJMoa1310345
Genovese, G., Friedman, D.J., Ross, M.D., et al. (2010) Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans. Science, 329, 841-845. https://doi.org/10.1126/science.1193032
Tzur, S., Rosset, S., Shemer, R., et al. (2010) Missense Mutations in the APOL1 Gene Are Highly Associated with End Stage Kidney Disease Risk Previously Attributed to the MYH9 Gene. Human Genetics, 128, 345-350. https://doi.org/10.1007/s00439-010-0861-0
Naik, R.P., Derebail, V.K., Grams, M.E., et al. (2014) Association of Sickle Cell Trait with Chronic Kidney Disease and Albuminuria in African Americans. JAMA, 312, 2115-2125. https://doi.org/10.1001/jama.2014.15063
O’Seaghdha, C.M., et al. (2011) The MYH9/APOL1 Region and Chronic Kidney Disease in European-Americans. Human Molecular Genetics, 20, 2450-2456. https://doi.org/10.1093/hmg/ddr118
Torres, V.E., et al. (2017) Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease. The New England Journal of Medicine, 377, 1930-1942. https://doi.org/10.1056/NEJMoa1710030
Levey, A.S., Becker, C. and Inker, L.A. (2015) Glomerular Filtration Rate and Albuminuria for Detection and Staging of Acute and Chronic Kidney Disease in Adults: A Systematic Review. JAMA, 313, 837-846. https://doi.org/10.1001/jama.2015.0602
Skorecki, K., Chertow, G.M., Marsden, P.A., Taal, M.W. and Yu, A.S.L. (2016) Brenner & Rector’s the Kidney. 10th Edition, Elsevier, Philadelphia.
Inker, L.A., et al. (2012) Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C. The New England Journal of Medicine, 367, 20-29. https://doi.org/10.1056/NEJMoa1114248
Shlipak, M.G., et al. (2013) Cystatin C versus Creatinine in Determining Risk Based on Kidney Function. The New England Journal of Medicine, 369, 932-943. https://doi.org/10.1056/NEJMoa1214234
End-Stage Renal Disease. Mayo Clinic, Mayo Foundation for Medical Education and Research. https://www.mayoclinic.org/diseases-conditions/end-stage-renaldisease/symptoms-causes/syc-20354532
Lieske, J.C., et al. (2013) A Reference System for Urinary Albumin: Current Status. Clinical Chemistry and Laboratory Medicine, 51, 981-989. https://doi.org/10.1515/cclm-2012-0768
Miller, W.G. and Bruns, D.E. (2009) Laboratory Issues in Measuring and Reporting Urine Albumin. Nephrology Dialysis Transplantation, 24, 717-718. https://doi.org/10.1093/ndt/gfp022
Witte, E.C., et al. (2009) First Morning Voids Are More Reliable than Spot Urine Samples to Assess Microalbuminuria. Journal of the American Society of Nephrology, 20, 436-443. https://doi.org/10.1681/ASN.2008030292
Inker, L.A., et al. (2014) KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for the Evaluation and Management of CKD. American Journal of Kidney Diseases, 63, 713-735. https://doi.org/10.1053/j.ajkd.2014.01.416
Whelton, P.K. and Carey, R.M. (2017) The 2017 Clinical Practice Guideline for High Blood Pressure. JAMA, 318, 2073-2074. https://doi.org/10.1001/jama.2017.18209
Fried, L.F., et al. (2013) Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy. New England Journal of Medicine, 369, 1892-1903. https://doi.org/10.1056/NEJMoa1303154
Guideline Development Group (2015) Clinical Practice Guideline on Management of Patients with Diabetes and Chronic Kidney Disease Stage 3b or Higher (eGFR https://doi.org/10.1093/ndt/gfv100
Shurraw, S., et al. (2011) Association between Glycemic Control and Adverse Outcomes in People with Diabetes Mellitus and Chronic Kidney Disease: A Population-Based Cohort Study. Archives of Internal Medicine, 171, 1920-1927. https://doi.org/10.1001/archinternmed.2011.537
Nathan, D.M., et al. (2013) Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study at 30 Years: Advances and Contributions. Diabetes, 62, 3976-3986. https://doi.org/10.2337/db13-1093
Williams, B., MacDonald, T.M,, Morant, S., et al. (2015) Spironolactone versus Placebo, Bisoprolol, and Doxazosin to Determine the Optimal Treatment for Drug-Resistant Hypertension (PATHWAY-2): A Randomised, Double-Blind, Crossover Trial. Lancet, 386, 2059-2068. https://doi.org/10.1016/S0140-6736(15)00257-3
Pitt, B., et al. (1999) The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure. New England Journal of Medicine, 341, 709-717. https://doi.org/10.1056/NEJM199909023411001
Zannad, F., et al. (2011) Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms. The New England Journal of Medicine, 364, 11-21. https://doi.org/10.1056/NEJMoa1009492
Ando, K., et al. (2014) Anti-Albuminuric Effect of the Aldosterone Blocker Eplerenone in Non-Diabetic Hypertensive Patients with Albuminuria: A Double-Blind, Randomised, Placebocontrolled Trial. The Lancet Diabetes and Endocrinology, 2, 944-953. https://doi.org/10.1016/S2213-8587(14)70194-9
Bakris, G.L., et al. (2015) Effect of Finerenone on Albuminuria in Patients with Diabetic Nephropathy: A Randomized Clinical Trial. JAMA, 314, 884-994. https://doi.org/10.1001/jama.2015.10081
Neal, B., et al. (2017) Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. The New England Journal of Medicine, 377, 644-657. https://doi.org/10.1056/NEJMoa1611925
Zinman, B., et al. (2015) Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. The New England Journal of Medicine, 373, 2117-2128. https://doi.org/10.1056/NEJMoa1504720
Kidney Disease: Improving Global Outcomes (KDIGO) Lipid Work Group (2013) KDIGO Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease. Kidney International Supplements, 3, 259-305.
Wanner, C. and Tonelli, M. (2014) KDIGO Clinical Practice Guideline for Lipid Management in CKD: Summary of Recommendation Statements and Clinical Approach to the Patient. Kidney International, 85, 1303-1309. https://doi.org/10.1038/ki.2014.31
Anderson, T.J., et al. (2016) 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. The Canadian Journal of Cardiology, 32, 1263-1282. https://doi.org/10.1016/j.cjca.2016.07.510
James, P.A., et al. (2014) 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report from the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA, 311, 507-520. https://doi.org/10.1001/jama.2013.284427
Yang, B., et al. (2018) Nephrotoxicity and Chinese Herbal Medicine. Clinical Journal of the American Society of Nephrology, 13, 1605-1611. https://doi.org/10.2215/CJN.11571017
Lazarus, B., et al. (2016) Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA Internal Medicine, 176, 238-246. https://doi.org/10.1001/jamainternmed.2015.7193
Muriithi, A.K., et al. (2014) Biopsy-Proven Acute Interstitial Nephritis, 1993-2011: A Case Series. American Journal of Kidney Diseases, 64, 558-566. https://doi.org/10.1053/j.ajkd.2014.04.027
Blank, M.-L., Parkin, L., Paul, C. and Herbison, P. (2014) A Nationwide Nested Case-Control Study Indicates an Increased Risk of Acute Interstitial Nephritis with Proton Pump Inhibitor Use. Kidney International, 86, 837-844. https://doi.org/10.1038/ki.2014.74
Perazella, M.A. and Markowitz, G.S. (2010) Drug-Induced Acute Interstitial Nephritis. Nature Reviews Nephrology, 6, 461-470. https://doi.org/10.1038/nrneph.2010.71
(2012) Notice. Kidney International Supplements, 2, 279. https://doi.org/10.1038/kisup.2012.37
Inker, L.A., et al. (2019) Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-Analysis in a Global Consortium. American Journal of Kidney Diseases, 73, 206-217. https://doi.org/10.1053/j.ajkd.2018.08.013
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group (1 (2017) KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney International Supplements, 7, 1-59. https://doi.org/10.1016/j.kisu.2017.04.001
Isakova, T., et al. (2017) KDOQI US Commentary on the 2017 KDIGO Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease—Mineral and Bone Disorder (CKD-MBD). American Journal of Kidney Diseases, 70, 737-751. https://doi.org/10.1053/j.ajkd.2017.07.019
de Brito-Ashurst, I., et al. (2009) Bicarbonate Supplementation Slows Progression of CKD and Improves Nutritional Status. Journal of the American Society of Nephrology, 20, 2075-2084. https://doi.org/10.1681/ASN.2008111205
Dobre, M., et al. (2013) Association of Serum Bicarbonate with Risk of Renal and Cardiovascular Outcomes in CKD: A Report from the Chronic Renal Insufficiency Cohort (CRIC) Study. American Journal of Kidney Diseases, 62, 670-678. https://doi.org/10.1053/j.ajkd.2013.01.017
Driver, T.H., et al. (2014) Low Serum Bicarbonate and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA). American Journal of Kidney Diseases, 64, 534-541. https://doi.org/10.1053/j.ajkd.2014.05.008
Mahajan, A., et al. (2010) Daily Oral Sodium Bicarbonate Preserves Glomerular Filtration Rate by Slowing Its Decline in Early Hypertensive Nephropathy. Kidney International, 78, 303-309. https://doi.org/10.1038/ki.2010.129
Keith, D.S., et al. (2004) Longitudinal Follow-up and Outcomes among a Population with Chronic Kidney Disease in a Large Managed Care Organization. Archives of Internal Medicine, 164, 659-663. https://doi.org/10.1001/archinte.164.6.659
Tangri, N., et al. (2011) A Predictive Model for Progression of Chronic Kidney Disease to Kidney Failure. JAMA, 305, 1553-1559. https://doi.org/10.1001/jama.2011.451
Chronic Kidney Disease Prognosis Consortium (2018) Grams ME, Sang Y, Ballew SH, et al, for the Chronic Kidney Disease Prognosis Consortium. Predicting Timing of Clinical Outcomes in Patients with Chronic Kidney Disease and Severely Decreased Glomerular Filtration Rate. Kidney Int. 2018; 93: 1442-1451. Kidney International, 94, 1025-1026. https://doi.org/10.1016/j.kint.2018.08.009
Eckardt, K.-U., et al. (2018) Improving the Prognosis of Patients with Severely Decreased Glomerular Filtration Rate (CKD G4+): Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney International, 93, 1281-1292. https://doi.org/10.1016/j.kint.2018.02.006
Cooper, B.A., et al. (2010) A Randomized, Controlled Trial of Early versus Late Initiation of Dialysis. The New England Journal of Medicine, 363, 609-619. https://doi.org/10.1056/NEJMoa1000552
Lameire, N. (2007) Handbook of Dialysis. In Daugirdas, J.T., Blake, P.G., Ing, T.S. Eds., OUP Academic, Oxford University Press, Oxford.
Couchoud, C.G., et al. (2015) Development of a Risk Stratification Algorithm to Improve Patient-Centered Care and Decision Making for Incident Elderly Patients with End-Stage Renal Disease. Kidney International, 88, 1178-1186. https://doi.org/10.1038/ki.2015.245
Tamura, M.K., et al. (2009) Functional Status of Elderly Adults before and after Initiation of Dialysis. The New England Journal of Medicine, 361, 1539-1547. https://doi.org/10.1056/NEJMoa0904655
Terasaki, P.I., Cecka, J.M., Gjertson, D.W. and Takemoto, S. (1995) High Survival Rates of Kidney Transplants from Spousal and Living Unrelated Donors. The New England Journal of Medicine, 333, 333-336. https://doi.org/10.1056/NEJM199508103330601